The cohort was established in 1967 by the Icelandic Heart Association; participants were followed up to six times. Baseline enrollment of 5764 men and women ran from 2002-2006; from 2007-2011 a follow-up exam was completed in 3,411 participants. Follow-up continues for hospitalizations, nursing home and home care assessments, and deaths. To study risk factors, prognosis, cause of death; and, uniquely, examine trajectories of health status and disease from middle to old age, this study of longitudinal change into old age has defined phenotypes for epidemiologic, genomic, and other omics analyses. A rich image and bio-repository has been developed for specimens that can be used for future novel research questions, thus maintaining the opportunities to test new hypotheses as they emerge. Together, these data provide a life-course perspective of disease and will enhance understanding of how health is maintained and disease develops over the lifetime. To date we have published widely on genetic and environmental risk factors for a range of common subclinical diseases in older persons, for example: atherosclerosis, coronary disease, and heart failure; osteoporosis, fractures and rheumatologic disease; obesity and glucose abnormalities; prevalence and risk factors for hearing and vision loss; brain structure and function, ADRD, and cerebral small vessel disease; and life style factors such as physical activity actigraphy and diet. We have also looked at cross associations among various systems, and shared underlying mechanisms such as inflammation, systemic vascular disease and metabolic dysregulation. Overall, the study has made important contributions to our understanding of the complexity and interrelationships amongst biologic systems in the trajectory towards old age. Our findings emphasize the need for a more systems-based approaches both to the study of, and clinical care for health and disease in old age. Specifically, for brain disease, this study has made important contributions to understanding the role of small vessel disease as both a consequence of cardiovascular risk factors and a substrate for cognitive impairment, dementia and depression. Work on the heart-brain and kidney-brain axes, which are all connected through small vessel disease, is in progress, as is continued research on the hemodynamic contribution to brain pathology. Data on the Off-spring of AD cases in AGES-RS is currently being analyzed to understand the genetic basis of the relation between AD and cardiovascular risk factors. This study has made a major contribution to understanding the genetic basis of a wide range of phenotypes, in the context of several international consortia. It also contributes to a NINDS sponsored consortia on plasma based biomarkers for vascular cognitive impairment, and to many other international consortia.